Chronotherapeutics: A Novel Approach in the Pharmacotherapy of Various Diseases

Most of the physiological functions of human body vary daily and this variation leads to changes in diseased state and in plasma drug concentration also. Due to the peak level of hormones in the body leads to disturbed sleep and increased pain. Human sleep activity cycle or solar/lunar adaptations depends on circadian rhythm and influenced by individual’s genetic makeup is responsible to affect the physiological functions.

The human circadian rhythm is also responsible for variation of physiological functions in certain diseased states such as depression, rheumatoid arthritis, myocardial infarction, peptic ulcer etc. Many body functions such as metabolism, sleep pattern, hormone production and physiology are regulated by changed environmental factors due to biological rhythms.

These physiological variations are predictable resonating dynamic systems, which require varied amount of drug at predictably different times within the circadian cycle in order to achieve maximum desired and minimum undesired therapeutic drug effect. To meet the therapeutics need of the treatment based on pathological diseases, chronotherapeutic drug delivery systems is the best alternative way to deliver the drug.

Some of the hormones such as estrogen and progesterone are released by the brain during the morning time, while melatonin and cortisol are released during sleep. The physiological abnormalities such as blood pressure and heart rate are highest during the morning hours and hence, most diseased symptoms occur during this period.

Cellular Senescence by the Epigenetic Regulators Inhibitor of Growth

Epigenetic and genetic factors are suggested to be involved in the aging process. Indeed, aging research on various model organisms like Caenorhabditis elegans or Drosophila melanogaster improved our understanding of genomic, epigenetic and proteomic aspects regarding the lifespan of these organisms. Specific set of genes or genetic loci that are related to longevity and aging are being analyzed in these model systems. Genetic and epigenetic factors appear to have significant influence also on human longevity, since the heritability of human lifespan was estimated in a range of 20-30% in many studies. Unlike genetics, epigenetics refers to “functional changes of the genome without changing the DNA sequence”. This includes chromatin changes and remodeling, which in general is triggered by factors that promote or remove histone modifications and regulate exchange of histone variants. However, the underlying mechanisms linking epigenetics to aging are poorly understood. One reason is the fact that aging is associated with a variety of human disorders, which includes cancer.

Interestingly, the gene encoding the epigenetic regulator tumor suppressor, inhibitor of growth 1 (ING1) has been suggested to be one of the aging-related candidate genes among 47 healthy individuals at the age of 85 years or older. Within this cohort, no aging-related diseases such as cancer, cardiovascular disease, pulmonary disease, diabetes, or Alzheimer disease have been diagnosed.

The ING tumor suppressors are localized in the nucleus and directly associated with chromatin regulation and control of gene expression. ING factors control various cellular pathways which include cell cycle control, DNA repair and two tumor protective pathways: apoptosis and cellular senescence that both seems to be important pathways for tumor suppression.